The Growth-Regulatory Role of p21 (WAF1/CIP1)

Abstract

Cyclin kinase inhibitors (CKIs) are proteins that bind to and inhibit the activity of cyclin-dependent kinases (Cdks). One of the first of these to be identified was p21, which binds and inhibits G, cyclin/Cdk complexes (Harper et al. 1993; Xiong et al. 1993). The p21 cDNA was cloned independently by several groups using a number of different screening strategies. It was identified as the product of a gene activated by wild-type p53, and it was named WAF1 (wild-type p53-activated factor (E1-Deiry et al. 1993). Microsequencing of a protein that interacted with Cdks led to its cloning using PCR (Xiong et al. 1993). Using a yeast two-hybrid screen, it was also identified as a Cdk-binding protein, and was subsequently named CIP1, for Cdk-interacting protein 1 (Harper et al. 1993). p21 was cloned using an expression screen designed to identify inhibitors of DNA synthesis from senescent fibroblasts, and it was named SDI1 (senescent cell-derived inhibitor (Noda et al. 1994). Using subtractive hybridization, the p21 cDNA was also isolated based on its increased expression in human melanoma cells that were induced to differentiate, and it was termed MDA-6, for melanoma differentiation associated protein (Jiang et al. 1994).